Capillary Nonperfusion in DR A Poor Predictor of Functional Loss

Retinal capillary nonperfusion plays a decisive role in diabetic retinopathy’s (DR) pathogenesis. However, this development may not be evident unless it is revealed by fundus fluorescein angiography (FA) or OCT angiography (OCT-A). To date, there is no therapy to prevent its occurrence or to revert it (i.e., achieve revascularization).  Considerable changes in retinal sensitivity in perfused and nonperfused areas occurred during the follow-up of up to two years, with lesser sensitivity deficits observed over time. Photo: Carolyn Majcher, OD. Click image to enlarge. A recent study published in JAMA Ophthalmology sought to learn more about the association between retinal capillary nonperfusion and sensitivity in DR. A research team from Belfast and London determined that, even though retinal capillary perfusion status was associated with function, sensitivity loss occurred in some perfused areas and normal function in some nonperfused areas. Also, the sensitivity deficit decreased over time (approximately 45% in the first year) despite poor glycemic control and high DR grades.“Retinal ischemia in DR is complex, and its impact on retinal function is nonuniform,” the study authors wrote in their paper.1This longitudinal cohort study, including people with moderate nonproliferative through non-high-risk proliferative diabetic retinopathy (n = 44), was conducted over a six-and-a-half-year period. It followed participants for up to two years. Mean participant age was 52.1 years, and 29% were women. Median hemoglobin A1c was 75.5mmol/mol (9.1% of total hemoglobin), and mean best-corrected visual acuity letter score was 85.7 (20/20Snellen equivalent).Mean retinal sensitivity deficit at baseline was associated with perfusion status, with larger deficits in nonperfused areas (n=354; 11.8dBs) compared to perfused areas (n=2,092; 6.6dB). Only age correlated positively with sensitivity deficit. A deficit of 5dB or greater occurred in 34% of perfused areas; 105 of 354 (30%) nonperfused areas had normal sensitivity. Rates of sensitivity deficit change in perfused and nonperfused areas from baseline to one year were -0.20dB/month and -0.28dB/month (perfused v.s nonperfused), respectively (1464 areas); from baseline to two years, rates were -0.16dB/month and -0.34dB/month (perfused vs. nonperfused), respectively (542 areas).1A commentary also published in JAMA Ophthalmology concurred with the authors that it is essential to report accurately both normal and abnormal retinal sensitivity deficits in both perfused and nonperfused areas over time.“However, the rate of change in sensitivity deficit of -0.03dB/year in the perfused compared with the nonperfused group may have been different but, clinically, the magnitude of the difference did not seem meaningful,” the commentary author wrote.2The author continued that the mean global changes of retinal sensitivity deficit of -1.7dB at one year and -2.8dB at two years were based on values obtained from 27 and 10 participants, respectively, so the point estimate findings undoubtedly have wide confidence intervals that reflect the likely true global change. Of these, only 12 and two participants, respectively, had at least severe nonproliferative DR, a surrogate for larger areas of retinal capillary nonperfusion.“It is difficult, if not impossible, to know how these few participants relate to the hundreds of thousands of individuals with this level of diabetic retinopathy around the world,” she noted.The commentary concluded that the hypotheses generated by the original study warrant replication and expansion to eyes with more severe DR cases and an adequate number of individuals that also address expected loss to follow-up after estimating a clinically meaningful difference in retinal sensitivity deficits.2Click here for the journal source and here for the commentary. 1. Hamilton-Perais J, Wright DM, Lim A, et al. Retinal sensitivity and retinal perfusion in diabetic retinopathy. JAMA Ophthalmol. October 30, 2025. [Epub ahead of print].2. Sivaprasad S. Retinal sensitivity in areas of retinal nonperfusion. JAMA Ophthalmol. October 30, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.